Inventors: Ronald Evans and Stanley Hollenberg
Potential Uses: Drug Discovery and Development

A screen for evaluation of antagonists of the steroid hormone superfamily or receptor proteins

The present invention relates to bioassays for evaluating compounds as potential antagonists for members of the steroid hormone superfamily of receptor protein(s). The invention bioassay comprises culturing test cells expressing steroid receptor protein in the presence of increasing concentrations of at least one compound whose ability to inhibit the action of agonists on members of the steroid hormone superfamily of receptors is sought to be determined, and a fixed concentration of at least one agonist for said steroid hormone receptor protein(s). Test cells employed in the practice of the present invention contain DNA which expresses a member of the steroid hormone superfamily of receptor protein(s) in a form having improved trans activation transcription activity, relative to wild type receptor, and a DNA sequence comprising a response element for said hormone receptor protein operatively linked to a reporter gene. Improved trans activation transcription activity is provided by receptor having a plurality of at least one parental receptor trans activation domain selected from tau-1 or tau-2, located outside the DNA binding and ligand binding domains of the receptor protein. The invention assay is completed by monitoring the level of expression of reporter gene product as a function of the concentration of potential antagonist compound in the culture medium, thereby indicating the ability of potential antagonist compound(s) to inhibit activation of members of the steroid hormone superfamily of receptors.